PROJECT SUMIVIARY (See instructions): We wish to continue our study of a new paradigm for the selective functionalization of complex molecules. Our approach is predicated on the development of fundamental reactions of functional groups that are ubiquitous in bioactive agents. The main emphasis of this proposal is the development of simple-to-make catalyst libraries that target functionalization of hydroxyl groups, amines and arene C-H bonds. Thus, the workhorse reactions we wish to develop are hydroxyl group transfer reactions (acylation, phosphorylation, sulfonylation and thiocarbonylation), amine group transfer reactions, and electrophilic aromatic substitutions. Each of these processes has been developed in our laboratory, and we wish to study these reactions in truly complex molecular arenas. Selective polyol derivatization reactions have value in and of themselves for natural product analog generation. Catalytic, site-selective amine functionalization within polyamines is virtually unknown, and we have initiated first steps for the development of these processes with a generalizable catalyst platform. So too of site-selective C-H bond functionalization in complex polycyclic arene-containing natural products. The significance of our overall goals may be in new catalysis principles, and in their application to the site-selective modification of complex, bioactive natural products. These studies extend fundamental studies of enantioselctivity to the less well-studied arena of regioselectivity. We now wish to expand greatly our studies ofthe selective derivatization of fascinating biological agents, including vancomycin and teicoplanin, as well as other complex antibiotics. In each case, we will continue to assess analogs for their novel antibiotic properties, hoping to extend further the exciting properties we have unearthed in the last couple years.